Evaluation of Cannabidiol for Reduction of Brain Neuroinflammation
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Changes in Neuroinflammation in the Thalamus
研究概览
简要总结
This study will investigate whether cannabidiol (CBD), the primary centrally and peripherally active non-intoxicating compound in the cannabis plant, exerts anti-neuroinflammatory effects in patients with chronic low back pain (cLBP) with or without mild-to-moderate depression.
详细描述
This is a randomized, double-blind, 2-arm mechanistic trial that seeks to assess the effects of CBD and placebo in patients with cLBP with and without mild-to-moderate depression, using integrated positron emission tomography / magnetic resonance imaging (PET/MRI) scans. The use of integrated PET/MRI will make it possible to simultaneously evaluate neuroinflammation (using [11C]PBR28, a second-generation radioligand for TSPO) and striatal function (using the Monetary Incentive Delay task, a validated fMRI task that probes behavioral and neural responses to rewards and losses).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 and ≤ 75;
- •The ability to give written, informed consent;
- •Fluency in English;
- •Average worst daily pain of at least 4 on a 0-10 scale of pain intensity, during a typical day. Pain needs to be present for at least 50% of days during a typical week;
- •On a stable pain treatment (pharmacological or otherwise) for the previous four weeks;
- •Diagnosis of chronic low back pain, ongoing for at least 6 months prior to enrollment.
- •High or mixed affinity binding to [11C]PBR28 identified by the Ala147Thr TSPO polymorphism in the TSPO gene (rs6971)
排除标准
- •Outpatient surgery within 2 weeks and inpatient surgery within 1 month of the time of scanning (this timeframe may be extended if they are not fully recovered from the surgery);
- •Elevated baseline transaminase (ALT and AST) levels above 3 times the Upper Limit of Normal (ULN), accompanied by elevations in bilirubin above 2 times the ULN;
- •Any interventional pain procedures within 6 weeks prior to scanning procedure or at any point during study enrollment;
- •Surgical intervention or introduction/change in opioid regimen at any point during study enrollment;
- •Contraindications to fMRI scanning and PET scanning (including presence of a cardiac pacemaker or pacemaker wires, metallic particles in the body, vascular clips in the head or previous neurosurgery, prosthetic heart valves, claustrophobia);
- •Implanted spinal cord stimulator (SCS) for pain treatment;
- •Any history of neurological illness or major medical illness, unless clearly resolved without long-term consequences;
- •Current or past history of major psychiatric illness (PTSD, depression, and anxiety are exclusion criteria only if the conditions were so severe as to require hospitalization in the past year);
- •Harmful alcohol drinking as indicated by an AUDIT score ≥ 16;
- •Pregnancy or breast feeding;
- •History of head trauma requiring hospitalization;
- •Major cardiac event within the past 10 years;
- •Regular use of recreational drugs in the past 3 months;
- •Use of cannabis-containing products, such as products containing THC or over the-counter or dispensary CBD, for 2 weeks prior to starting the study medication and during the 4 weeks of taking the study medication;
- •Use of immunosuppressive medications, such as prednisone, TNF medications within 2 weeks of the visit;
- •Current bacterial or viral infection likely affecting the central nervous system;
- •Use of the medications valproate and clobazam, which may increase risk of hepatic AEs;
- •Safety concerns related to use of any of the following medications will be discussed on an individualized basis with a physician:
- •Strong and moderate CYP3A4 inhibitors including boceprevir, cobicistat, conivaptan, danoprevir, elvitegravir, ritonavir, indinavir, itraconazole, ketoconazole, lopinavir, paritaprevir and ombitasvir and/or dasabuvir, posaconazole, saquinavir and telaprevir, tipranavir, clarithromycin, diltiazem, idelalisib, nefazodone, nelfinavir, troleandomycin, voriconazole, aprepitant, cimetidine, ciprofloxacin, clotrimazole, crizotinib, cyclosporine, dronedarone, erythromycin, fluconazole, fluvoxamine, imatinib, tofisopam, disulfiram, and verapamil;
- •Strong and moderate inhibitors of CYP2C19 including fluoxetine and ticlopidine;
- •Sensitive and moderately sensitive substrates of CYP2C19 including clobazam, lansoprazole, omeprazole, S-mephenytoin, and rabeprazole;
- •Sensitive and moderately sensitive substrates of CYP1A2 including alosetron, duloxetine, ramelteon, tasimelteon, theophylline, tizanidine, pirfenidone, and ramosetron;
- •Sensitive and moderately sensitive substrates of CYP2B6 including bupropion and efavirenz;
- •Sensitive and moderately sensitive substrates of CYP2C8 including repaglinide, montelukast, pioglitazone, and rosiglitazone;
- •Sensitive and moderately sensitive substrates of CYP2C9 including tolbutamide, celecoxib, glimepiride, and warfarin;
- •Sensitive and moderately sensitive substrates of UGT1A9 including diflunisal, propofol, and fenofibrate;
- •Sensitive and moderately sensitive substrates of UGT2B7 including, gemfibrozil, lamotrigine, and morphine;
- •CNS depressants including all antipsychotics, benzodiazepines (except for alprazolam, clonazepam, and lorazepam, which have low binding affinity to TSPO44-48), and non-benzodiazepine sleep aids that have a known unsafe reaction with CBD;
- •Use of opioids ≥ 30 mg morphine equivalents on average per month;
- •Actively suicidal, history of suicide attempt or an aborted attempt within the last 5 years, or engagement in non-suicidal self-injurious behavior within the last year;
- •Allergy to sesame oil, and any other ingredients of EPIDIOLEX;
- •Any other contraindications to CBD administration noted by the study physician;
- •Any significant change in drug use and pain treatment from screening visit;
- •In the opinion of the investigators, unable to safely participate in this study and/or provide reliable data (e.g., unable to reliably rate pain; unlikely to remain still during the imaging procedures, etc).
研究组 & 干预措施
Cannabidiol (CBD)
The recommended starting dosage is 2.5mg/kg taken twice daily. The titration schedule recommended in the EPIDIOLEX label will be followed, with 2.5 mg/kg twice daily in week 1, 5 mg/kg twice daily in week 2, 7.5 mg/kg twice daily in week 3, and 10 mg/kg twice daily in week 4 with the second PET scan conducted after one week at the maximum labeled dose. Any participant not tolerating a given dose can either go back down to the next lowest dose or delay uptitration at any week in the protocol. Participants will be instructed to take Epidiolex with a meal rather than in a fasted state. Participants will be treated for 4 weeks in total.
干预措施: CBD (Drug)
Placebo
The placebo will be taken at identical doses to the active drug condition.
干预措施: Placebo (Other)
结局指标
主要结局
Changes in Neuroinflammation in the Thalamus
时间窗: Change from Baseline to Week 4
The investigators will test for the presence of a significant treatment effect in the brain \[11C\]PBR28 signal in the thalamus, in order to test whether patients in the CBD arm will demonstrate significantly larger treatment-related reductions in neuroinflammation, compared to patients in the placebo arm.
次要结局
- Changes in Neuroinflammation in Limbic Regions(Change from Baseline to Week 4)
- Change in Clinical Pain Ratings(Change from average score during the 7 days prior to treatment (Baseline) to average score during the final week of treatment)
- Change in Pain Bothersomeness(Change from average score during the 7 days prior to treatment (Baseline) to average score during the final week of treatment)
- Correlation Between Reductions in Thalamic [11C]PBR28 PET Signal and Reductions in Clinical Pain Ratings(Change from Baseline to Week 4)
- Correlation Between Reductions in Limbic [11C]PBR28 PET Signal and Reductions in Depressive Symptoms(Change from Baseline to Week 4)
- Change in Depressive Symptoms(Change from Baseline to Week 4)
- Patient Global Impression of Change(Week 4)
研究者
Jodi Gilman
Associate Professor
Massachusetts General Hospital